Proteomics of the ascitic fluid for the differentiation of advanced ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15510-e15510
Author(s):  
Gururao Hariprasad ◽  
Roopa Hariprasad ◽  
Lalit Kumar ◽  
Amit Kaushik ◽  
Alagiri Srinivasan

e15510 Background: Ovarian cancers are classified as primary, if it arises in the ovary and secondary or metastatic, if the origin is from other parts of the body. The clinical manifestations of these cancers in the advanced stage are very similar making it difficult to distinguish clinically, hiostopathologically and radiologicaly. The therapeutics and management of the primary and secondary malignancies are completely different. While, the advanced primary malignancies are treated by cytoreduction followed by chemotherapy, the metastatic tumors are treated mainly with palliative chemotherapy. The prognosis is better for primary than secondary ovarian cancer making their diagnosis very crucial for patient care. Methods: 1D and 2D-gel based proteomic approaches were used to study the differentially expressed proteins in the ascitic fluid of patients (10 primary and 4 secondary) with advanced ovarian cancer. The relative ratios of the protein expression were estimated by densitometric analysis. The bands/spots with more than three fold difference were subjected to in-gel trypsin digestion and identified by mass spectrometric analysis. The differential expression of one of the proteins was further validated by western blot experiments and ELISA. Results: Programmed Cell Death 1-Ligand 2 and apolipoprotein A1 were seen to be up regulated in the advanced primary ovarian cancer while apolipoprotein A4, and chain L, humanized version of the anti-human fas antibody Hfe7a were seen to be up regulated in the metastatic variant. Validation for the expression of apolipoprotein A1 shows that a 61.8ng/ml cut off is ideal to differentiate the primary and secondary advanced ovarian cancers. The assay has 100% sensitivity, 75% specificity, positive predictive value of 90.9%, negative predictive value of 100%, accuracy of 92.85% and a pre-test odds positive of 2.5. Conclusions: Proteomics of ascitic fluid is useful for the differentiation of advanced ovarian cancers. There are proteins which are differentially expressed in the ascitic fluid of patients with primary and secondary ovarian cancer. Apolipoprotein A1 is a potential biomarker that can be used to differentiate the closely mimicking clinical scenarios of advanced ovarian cancer.

Biomarkers ◽  
2013 ◽  
Vol 18 (6) ◽  
pp. 532-541 ◽  
Author(s):  
Gururao Hariprasad ◽  
Roopa Hariprasad ◽  
Lalit Kumar ◽  
Alagiri Srinivasan ◽  
Srujana Kola ◽  
...  

2019 ◽  
Vol 37 (9) ◽  
pp. 440-452 ◽  
Author(s):  
Luděk Záveský ◽  
Eva Jandáková ◽  
Vít Weinberger ◽  
Luboš Minář ◽  
Veronika Hanzíková ◽  
...  

2021 ◽  
Author(s):  
Olivia Le Saux ◽  
Hélène Vanacker ◽  
Fatma Guermazi ◽  
Mélodie Carbonnaux ◽  
Clémence Roméo ◽  
...  

Homologous recombination deficiency and VEGF expression are key pathways in high-grade ovarian cancer. Recently, three randomized practice changing trials were published: the PAOLA-1, PRIMA and VELIA trials. The use of PARP inhibitors (PARPi) following chemotherapy has become standard of care in first line. Combination of PARPi with anti-angiogenic agents has demonstrated synergistic activity in preclinical study. This review summarizes the body of evidence supporting the efficacy and safety of the combination of PARPi and anti-angiogenic drugs in first-line homologous recombination deficiency high-grade ovarian cancer leading to US FDA and EMA approvals. This double maintenance is supported by: a large benefit with bevacizumab + olaparib compared with olaparib alone, a rationale for additive effect, and a good safety and cost-effective profile.


1987 ◽  
Author(s):  
O Wilhelm ◽  
A Henschen ◽  
R Hafter ◽  
H Graeff

Crosslinked fibrin has been demonstrated by immunohistochemi-cal tests to occur around tumor plugs, on the surface and in the stroma of the tumor in ovarian cancer. High levels of D-Dimer (200-800μg/ml), the characteristic terminal degradation product of crosslinked fibrin, are found in ascitic fluid of patients with advanced ovarian cancer. These findings suggest that fibrin polymerisation and degradation are related to and even may influence tumor growth. The kind of proteases which are responsible for degradation of crosslinked fibrin is, however, unknown.lt was the aim of this study to evaluate whether plasmin and/or other proteases are involved in tumor-associated fibrinolysis. Therefore the total high-molecular-weight fibrin degradation products in ascitic fluid were purified by protamine sulfate precipitation, gel filtration, immunoadsorption and compared with the components of plasmin-degraded crosslinked fibrin, i.e. DD,DY,YX,DXD and DXY, by direct SDS-PAGE in the absence of mercaptoethanol and after excision of the bands, mercaptolysis and re-electrophoresis. Pronounced similarity between the two sets of fragments was observed. For further information the fragments from the two sources were mercaptolysed and their polypeptide chain components separated by reversed-phase high-performance liquid chromatography, the components being identified by N-terminal sequence analysis and SDS-PAGE. Highly similar patterns were obtained and components corresponding to γ-γ ,γ-γ1, β, β2 and α1 could be recognized. The findings provide strong evidence for plasmin being the primary protease involved in ovarian carcinoma-related fibrinolysis, (supported by Deutsche Forschungsgemeinschaft.SFB 207, A2).


1993 ◽  
Vol 54 (1) ◽  
pp. 38-44 ◽  
Author(s):  
Ronald E. Hempling ◽  
M. Steven Piver ◽  
Nachimuthu Natarajan ◽  
Trudy R. Baker ◽  
John M. Thompson ◽  
...  

2020 ◽  
Author(s):  
Shahan Mamoor

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2,3). We previously identified forkhead box L2 (4), (FOXL2) as among the genes whose expression was most different in HGSC ovarian tumors when compared to the ovary. Here, we find that potential FOXL2 transcriptional target (5,6) odd-skipped related gene OSR2 (7) is differentially expressed in high-grade serous ovarian cancer, and could be observed in independent tumor microarray data (2,3). These data reveal perturbed expression of a target gene of a key transcription factor and specifier of ovarian cell fate in high-grade serous ovarian cancers.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Hu ◽  
Liuxing Wu ◽  
Ben Liu ◽  
Kexin Chen

The incidence of adenocarcinoma of the esophagogastric junction (AEG) has markedly increased worldwide. However, the precise etiology of AEG is still unclear, and the therapeutic options thus remain limited. Growing evidence has implicated long non-coding RNAs (lncRNAs) in cancer immunomodulation. This study aimed to examine the tumor immune infiltration status and assess the prognostic value of immune-related lncRNAs in AEG. Using the ESTIMATE method and single-sample GSEA, we first evaluated the infiltration level of 28 immune cell types in AEG samples obtained from the TCGA dataset (N=201). Patients were assigned into high- and low-immune infiltration subtypes based on the immune cell infiltration’s enrichment score. GSEA and mutation pattern analysis revealed that these two immune infiltration subtypes had distinct phenotypes. We identified 1470 differentially expressed lncRNAs in two immune infiltration subtypes. From these differentially expressed lncRNAs, six prognosis-related lncRNAs were selected using the Cox regression analysis. Subsequently, an immune risk signature was constructed based on combining the values of the six prognosis-associated lncRNAs expression levels and multiple regression coefficients. To determine the risk model’s prognostic capability, we performed a series of survival analyses with Kaplan–Meier methods, Cox proportional hazards regression models, and the area under receiver operating characteristic (ROC) curve. The results indicated that the immune-related risk signature could be an independent prognostic factor with a significant predictive value in patients with AEG. Furthermore, the immune-related risk signature can effectively predict the response to immunotherapy and chemotherapy in AEG patients. In conclusion, the proposed immune-related lncRNA prognostic signature is reliable and has high survival predictive value for patients with AEG and is a promising potential biomarker for immunotherapy.


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